There are certain thought barriers involved in making
diagnostic-classification criteria in diseases of unknown origin. Among
these are a lack of appreciation of the issue of circular logic, the
basic oneness of diagnostic and classification criteria, the lack of
appreciation as to why we make such criteria in the first place, and the
lack of importance informing our patients that we do as well as should
treat them without a firm diagnosis in many instances. The relevance of
these thought barriers to the new American College of
Rheumatology/European Union League Against Rheumatism (ACR/EULAR)
Rheumatoid Arthritis (RA) classification criteria are also discussed.

In a series of talks and papers about methodology, I had already
talked and written (1) about one popular pastime of our profession, that
of making diagnostic or classification criteria for diseases of unknown
etiology and pathogenesis. This is obviously very pertinent when we have
yet to discern distinct causes for a majority of major illnesses that we
currently manage. What brings me back to the same issue is 1. on
reflecting back, perhaps I was not clear enough about why I considered
diagnosis and classification as basically the same, and 2. since my last
paper, the new ACR/EULAR classification criteria for RA has appeared,
(2-4) a critical look at which will perhaps better explain my
objectives.

I had underlined in a previous paper (1) that diagnosis and
classification are on a continuum. To me, there is actually no
difference in the mental or mathematic activity in the formulation of
criteria for diagnosis, classification or both. Diagnosis is
classification in the individual patient. (1) The comparison groups, the
odds ratios, and the pre-test probabilities are the essential components
of the mental process. Again, as I had emphasized the pre-test (or
diagnostic criteria) probabilities are the two most essential components
of whether we would name a set of criteria as diagnostic or
classification. Perhaps a further look into the origins of the two words
will better clarify the issue.

The verb "to diagnose" is originally Greek, and it means
"to discern." Thus, it also has the connotation of
"understanding the nature of." The verb "to
classify," on the other hand, is more contemporary. It simply means
to allocate into classes. As such, it implies less precision and perhaps
less of an attempt "to better comprehend the nature of." When
confronted with a patient, we prefer to diagnose and when we do
research, we like to classify. However, I respectfully suggest that this
is a bit of double talk. I suggest that there is no sound reason to say
that we have to be more precise in making a diagnosis in every day
practice as compared to when we enroll a patient into a drug trial.

As the traditional healer, we are of the opinion that the patient
expects a diagnosis rather than a classification from us. This is
perhaps, we still maintain, as our predecessors of the previous
centuries did, ours is a profession of "omniscience." We all
like to give a patient a diagnosis; in other words, we are not content
with a classification only-we also want to attach perhaps an
"omniscience" to what we classify. On the other hand, we as
rheumatologists painfully know that while we do not know the exact
nature of many of the illnesses we recognize and manage, more recently
and happily, we have been rather successful in their management. This
brings me directly to the issue of the new ACR/EULAR criteria.

I am concerned there is much that is critical that needs to be said
about the new RA criteria. The whole exercise starts with a group of
experts from each side of the Atlantic. The experts are of even number
and similar gender distribution between these different sides of the
Atlantic. This emphasis by the ACR/EULAR on equal numbers across
continents and gender suggests that the data is therefore more accurate.
This message might indeed impress the third-party payers or the policy
makers in Washington, D.C. or Brussels but surely is out of context in a
rheumatology journal. Are there data that indicate that one nationality
or gender is different from their counterparts in managing RA?

Also the related manuscripts fail to address the nagging question
of how many patients in daily practice with psoriasis and early onset
arthritis are diagnosed as psoriatic arthritis when they present, while
they eventually turn out to have RA in the months following. Similarly,
how many young females with synovitis of the small joints of the hand,
Reynaud's phenomenon, and a positive ANA are initially diagnosed
with systemic lupus erythematosus (SLE) and, in time, turn out to have
erosive RA?

There are still other important issues related to the way a
consensus was reached in assessing the disease severity, actually
showing pronounced variance among the paper patients. Furthermore, when
validity estimations were made, the reader was not given formal
statistics that compared disease severity between, this time actual,
patients from different cohorts. However, I will digress here from the
ACR/EULAR RA criteria and try to make a list of thought barriers in
criteria making for diseases of unknown origin. They surely apply to the
ACR/EULAR example at hand.

As depicted in Table 1, the first issue is trying to avoid
circularity in thinking. This is unrealistic. Fries indicated such many
years ago (5):

I will go even further and suggest that all diagnoses and
classifications, even when specific histology and microbiology are
involved, are based on definitions and, thus, have some
"circularity." However, circular reasoning is only present
when the conclusion is nothing more than a reiteration of the premise(s)
of the reasoning. The following set of statements can be considered in
this regard:

1. Our rheumatology unit does not make a diagnosis of RA unless
symptoms continue for 3 months after their onset.

2. Among 180 patients with new inflammatory arthritis followed up
to 3 months, the arthritis went away after symptomatic therapy in 120
patients.

3. It was interesting to note that there were no patients with RA
among these 120 patients responding to symptomatic therapy.

This is clearly circular logic. It was no surprise that the
rheumatologists in this setting did not see any patients with RA. The
rule in their clinic was that 3 months had to pass after the initial
symptoms for a patient to have RA. However, none of the 120 patients was
followed for longer than 3 months.

2. Among 1,000 new patients seen in our clinic within a year, 490
satisfied this definition.

3. Almost half of the new patients we see in a year have RA.

There is nothing circular in the above statements. First, a
rheumatology unit defined a condition. Then, they observed a number of
patients fulfilling that condition within a certain time interval. They
finally concluded that they saw the X-number of patients who fulfilled
their definition within the time period specified.

In brief:

* Coming to a conclusion unaware that the conclusion reached was
inescapable is "circular logic."

* To search for and find what has been defined is NOT circular
logic.

The second thought barrier as listed in Table 1 is the
"promise of a diagnostic criteria as distinct from classification
criteria." I had addressed this issue in some detail in my previous
paper. (1) Since then and predictably, the new ACR/EULAR criteria also
make the point that separate criteria are needed for diagnosis. Again,
appealing to Dr. Fries (6):

I would suggest that not conceptually but in reality diagnosis and
classification are the same; however, it should be added that neither
can be universal, in other words "good for all purposes."
This, in turn, takes us to the third and fourth points in Table 1.

In my previous paper on classification, (1) I attempted to explain
that what really transforms a set of classification criteria to that of
diagnostic criteria is mainly two-fold: 1. Why do we want to diagnose or
classify? and 2. What is the pre-test probability of the conditions we
wish to classify or diagnose? These are also exactly the third and
fourth issues in the table. As explained in the previous paper, and as I
will further discuss when I go back to the ACR/EULAR RA criteria
shortly, there can be many reasons for making criteria for
classification or diagnosis. We can make such criteria for disease
prevention, management, and allocation of resources, as well as for
clinical or laboratory research. While we do this, the pretest odds will
differ according to geography, subspecialty, disease course, and the
curiously uniformly forgotten issue of yet undefined diseases. Any
criteria making, by definition, needs suitable comparison or control
groups. How does one include a yet undefined disease in a control group?
This is one important reason why a specificity of 100% is most rare in
any biological research.

The last point on Table 1 will, I think is better appreciated in
the context of how the remaining points are relevant to the new
ACR/EULAR criteria for RA. The issues of the ungrounded fear of
circularity and the promise of diagnostic criteria, as distinct from
classification criteria, yet to come, are explicitly present in the
related manuscripts. However, my most important criticism of the said
criteria is the fact that they are not criteria for diagnosing or RA.
They are, in fact, criteria for the question "When and if to start
methotrexate in a patient with early onset inflammatory arthritis?"
The whole design of this criteria exercise was to this end. This being
so, I venture to suggest that it was the barrier no. 4 in Table I that
was the culprit.

Disclosure Statement

This work has been partially sponsored by the Turkish Academy of
Sciences. The author has no further financial or proprietary interest in
the subject matter or materials discussed, including, but not limited to
employment, consultancies, stock ownership, honoraria and paid expert
testimony.

Presence of disease "criteria" affirms or ignorance of the essence
of disease. If we understand a disease, we can ascribe the elements
that are necessary and sufficient for its diagnosis. One can so
define gouty arthritis, in which joint fluid crystals serve as a
"gold standard" against which to measure the usefulness of other
observations. No other major rheumatic disease, including SLE, has
such a standard. Thus, criteria must be constructed in a circular
manner, by testing variables against a diagnosis based on intuition
[emphasis added]. The "best" criteria therefore only describe the
current conventional wisdom in an efficient manner.

Conceptually, the classification criteria are the same as
diagnostic criteria, and in a perfect world, might indeed
be named diagnostic criteria. That is, if sensitivity
and specificity were both 100%, classification criteria
would be diagnostic criteria and would apply to every
individual case.

Table 1 Thought Barriers in Criteria Making
1. The misconception of trying to avoid circularity in
criteria making
2. Promise of diagnostic criteria, somehow different from
classification criteria, to come
3. A lack of consideration of why and how should we
diagnose
4. A lack of appreciation of pre- and posttest (criteria) odds
5. A lack of consideration that we should perhaps involve
our patients in naming and what we plan to do with their
diagnosis(es)